1. Field
Provided are a device and a method of separating cells by using a magnetic force, and more particularly, a device and a method of efficiently separating target cells from other cells by simultaneously generating a magnetic force, and a force applied in the opposite direction of the magnetic force.
2. Description of the Related Art
A cell is a basic unit of an animal's body, and organs in the body include different types of cells. In general, biopsies have been used to diagnose various diseases. However, due to the recent improvement in the accuracy of cytology, diseases can be simply and precisely diagnosed by using cytology. Particularly, as patients may avoid unnecessary biopsies, a lot of attention has been paid to the use of cytology for precise diagnosis.
A target cell needs to be extracted from a sample for cytology. A target cell can be separated from a solid tissue by figuring out the location of the target cell using a microscope. However, since bodily fluid (e.g., blood) contains various cells, it is difficult to separate a target cell therefrom. Since various cells or substances related to diseases are mixed in blood, it is essential to separate a target cell from a fluid such as blood in which various cells are mixed, and remove undesired cells.
In particular, research into cancer cells in blood has received much attention. Malignant tumor-related deaths are generally caused by metastasis by which tumors spread to distant organs or tissues. Accordingly, early detection of tumors and monitoring the growth of the tumors are important for successfully treating cancers. Histopathology has been used to diagnose cancers. Histopathology is a method used for analyzing tumors using a sample from a living tissue. Such a histopathological approach requires a direct observation of tumor cells. However, tumors may not exist at a location of a tissue selected to obtain a living sample. In addition, data from only a specific location in the living sample can be obtained, and thus it is difficult to know whether tumors are metastasized to other locations.
It is known that cell circulating tumor cells (“CTCs”) can be detected in patients before tumor cells are initially detected. Thus, the CTCs may be used for early detection and prediction of cancers. Furthermore, since most cancers are metastasized via blood, the CTCs may be used as a marker for the metastasis of cancers. In addition, if the CTCs are detected after removing cancer cells by surgery, a cancer relapse may be detected. However, it is difficult to detect the existence and number of the CTCs since the content of the CTCs is very low in blood and the CTCs are fragile. Therefore, there is a need to develop a highly sensitive diagnosis method for detecting CTCs, cancer cells, or cancer stem cells contained in a patient's body. For this, a method of efficiently separating tumor cells contained in a biological sample and a device therefore are required.
Recently, magnetic separation techniques using a magnetic force have been used in the fields of medical & bio technology in various ways. Much attention has been paid to magnetic separation techniques due to scalability, efficiency, simplicity, simple conditions, automation, and low costs. According to magnetic separation techniques, a sample is cultured using magnetic particles that have high affinity to a target material and are sensitive to a magnet. In a separation method using such a magnetic force, micro particles or beads having a diameter in the range of about 10 nanometers (nm) to about 20 micrometers (μm) are used.
According to general magnetic separation techniques, when only a magnetic force of the magnet is applied, the target materials or cells which are marked with the magnetic particles are pulled toward the magnet by the magnetic force, however, other cells also move by a flow generated while cells marked with magnetic particles move due to the magnetic force, and may be trapped. Thus, a cell separation ratio may decrease and false-positiveness may increase when only the magnetic force is applied. Furthermore, since the other cells undesirably move by the flow generated while marked cells move when only a magnetic force of the magnet is applied, a separate washing process is required to remove non-specifically bound cells, and thus the target cells may also be washed or cell membranes may be damaged by shear stress generated during the washing process, thereby increasing cell loss.